Effect of the Tocotrienol-Rich Fraction (TRF) on the Healthspan of Caenorhabditis elegans

Vitamin E is an established antioxidant. However, the effect of vitamin E on healthspan, which deteriorates during ageing, has not been determined because most related studies have emphasized its effects on lifespan. Therefore, the purpose of this study was to determine the effect of palm tocotrienol-rich fraction (TRF) on the lifespan, locomotion and thermotolerance of Caenorhabditis elegans, which share many common gene sequences with humans. The nematodes were treated with different concentrations of TRF (0 - 200 μg/mL), and the number of surviving nematodes at each concentration (N=30, duplicate) was counted daily under a light microscope to determine the optimal dose of treatment. The nematodes were divided into 3 groups, namely; control, Tween-80 (vehicle) and TRF-treated. Locomotion and thermotolerance were determined on day 4 and 12 of treatment in adult nematodes. ImageJ was used for locomotion analysis, and thermotolerance was determined based on nematode survivals after exposure to 37 °C. TRF-treated C. elegans had significantly longer lifespans compared to controls (P = 0.003). The TRF group (50 μg/mL) had the longest mean lifespan (23.5 days), which was significantly longer compared to controls, (18.5 days; (P = 0.002). However, locomotion was similar between all groups. In the thermotolerance assay, the survival determined on day 4 and day 12 of TRF-treatment was higher compared to controls (P= 0.046). Interestingly, the Tween- 80-treated group showed similar results as the TRF-treated group compared to controls. The findings indicate that TRF prolongs the lifespan and increases the thermotolerance of C. elegans but does not improve the locomotion of the worms as they age.

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Supplementation with Natural Forms of Vitamin E Augments Antigen-Specific TH1-Type Immune Response to Tetanus Toxoid

BioMed Research International ◽

10.1155/2013/782067 ◽

2013 ◽

Vol 2013 ◽

pp. 1-8 ◽

Cited By ~ 10

Author(s):

Ammu Kutty Radhakrishnan ◽

Dashayini Mahalingam ◽

Kanga Rani Selvaduray ◽

Kalanithi Nesaretnam

Keyword(s):

Immune Response ◽

Vitamin E ◽

Mouse Model ◽

Tetanus Toxoid ◽

Treated Group ◽

Alpha Tocopherol ◽

Natural Forms ◽

Tocotrienol Rich Fraction ◽

Th1 Immune Response

This study compared the ability of three forms of vitamin E [tocotrienol-rich fraction (TRF), alpha-tocopherol (α-T), and delta-tocotrienol (δ-T3)] to enhance immune response to tetanus toxoid (TT) immunisation in a mouse model. Twenty BALB/c mice were divided into four groups of five mice each. The mice were fed with the different forms of vitamin E (1 mg) or vehicle daily for two weeks before they were given the TT vaccine [4 Lf] intramuscularly (i.m.). Booster vaccinations were given on days 28 and 42. Serum was collected (days 0, 28, and 56) to quantify anti-TT levels. At autopsy, splenocytes harvested were cultured with TT or mitogens. The production of anti-TT antibodies was augmented (P<0.05) in mice that were fed withδ-T3 or TRF compared to controls. The production of IFN-γand IL-4 by splenocytes from the vitamin E treated mice was significantly (P<0.05) higher than that from controls. The IFN-γproduction was the highest in animals supplemented withδ-T3 followed by TRF and finallyα-T. Production of TNF-αwas suppressed in the vitamin E treated group compared to vehicle-supplemented controls. Supplementation withδ-T3 or TRF can enhance immune response to TT immunisation and production of cytokines that promote cell-mediated (TH1) immune response.

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AVALIAÇÃO DA ATIVIDADE NEMATICIDA E OVICIDA DO ÓLEO ESSENCIAL DE Foeniculum vulgare EM Caenorhabditis elegans

10.51189/rema/1102 ◽

2021 ◽

Author(s):

Wanderson Anjos Da Silva ◽

Yulli Roxenne Albuquerque ◽

Gustavo Palombo Otaviano ◽

Ricardo de Oliveira Correia ◽

Fernanda de Freitas Anibal

Keyword(s):

Caenorhabditis Elegans ◽

Tween 80 ◽

Foeniculum Vulgare ◽

C Elegans

Introdução: As infecções causadas por geo-helmintos afetam humanos, plantas e animais, trazendo preocupação para a saúde pública e para o setor agropecuário. O desenvolvimento de resistência relatada em helmintos parasitas frente aos antiparasitários trouxe a necessidade de buscar novos agentes terapêuticos como alternativa aos fármacos já existentes. Objetivo: Avaliar as atividades antinematódeas do óleo essencial de Foeniculum vulgare (funcho-doce), utilizando o nematódeo Caenorhabditis elegans como modelo biológico. Material e métodos: O óleo essencial comercial de F. vulgare foi testado nas concentrações de 0,5%, 0,25%, 0,13%, 0,06%, 0,03% e 0,01% (v/v). O solvente do óleo (Tween 80) foi utilizado como controle negativo, enquanto o controle positivo foi realizado com Levamisol a 25 mM. Os ensaios foram realizados em triplicata e em três momentos diferentes (n=9), avaliando por microscopia óptica a quantidade de nematódeos vivos e a motilidade nos períodos de 6h, 24h e 48h de exposição ao óleo essencial. Posteriormente, foram realizados ensaios analisando os efeitos ovicida, pela inibição da eclosão das larvas após 24h de exposição. Para a identificação dos componentes do óleo foi realizada a cromatografia gasosa acoplada à espectrometria de massa. Resultados: O óleo de F. vulgare apresentou redução significativa (p<0,05) de nematoides vivos e de eclosão das larvas dos ovos a partir da concentração de 0,06%, além de uma redução acentuada na motilidade. Nas concentrações de 0,13% e 0,25% observou-se a redução de mais de 50% de nematódeos vivos, enquanto no tratamento com 0,5% não foi observada a presença de nematódeos vivos a partir do período de 6h. A caracterização química do óleo identificou o anetol (89%) como composto majoritário. Conclusão: O óleo essencial de F. vulgare apresentou atividades nematicida e ovicida em C. elegans, sendo este efeito possivelmente causado pelo composto anetol, e desta maneira possui potencial para ser utilizado no desenvolvimento de novas terapias antihelmínticas.

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The glycomes of Caenorhabditis elegans and other model organisms

Biochemical Society Symposium ◽

10.1042/bss0690117 ◽

2002 ◽

Vol 69 ◽

pp. 117-134 ◽

Cited By ~ 47

Author(s):

Stuart M. Haslam ◽

David Gems ◽

Howard R. Morris ◽

Anne Dell

Keyword(s):

Caenorhabditis Elegans ◽

Current Knowledge ◽

Structural Data ◽

Model Organisms ◽

Entire Genome ◽

C Elegans ◽

The Face ◽

Area Of Concern ◽

Nematode Worm

There is no doubt that the immense amount of information that is being generated by the initial sequencing and secondary interrogation of various genomes will change the face of glycobiological research. However, a major area of concern is that detailed structural knowledge of the ultimate products of genes that are identified as being involved in glycoconjugate biosynthesis is still limited. This is illustrated clearly by the nematode worm Caenorhabditis elegans, which was the first multicellular organism to have its entire genome sequenced. To date, only limited structural data on the glycosylated molecules of this organism have been reported. Our laboratory is addressing this problem by performing detailed MS structural characterization of the N-linked glycans of C. elegans; high-mannose structures dominate, with only minor amounts of complex-type structures. Novel, highly fucosylated truncated structures are also present which are difucosylated on the proximal N-acetylglucosamine of the chitobiose core as well as containing unusual Fucα1–2Gal1–2Man as peripheral structures. The implications of these results in terms of the identification of ligands for genomically predicted lectins and potential glycosyltransferases are discussed in this chapter. Current knowledge on the glycomes of other model organisms such as Dictyostelium discoideum, Saccharomyces cerevisiae and Drosophila melanogaster is also discussed briefly.

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Cytoprotective Effect of Tocotrienol-Rich Fraction and α-Tocopherol Vitamin E Isoforms Against Glutamate-Induced Cell Death in Neuronal Cells

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000201 ◽

2014 ◽

Vol 84 (3-4) ◽

pp. 0140-0151 ◽

Cited By ~ 11

Author(s):

Thilaga Rati Selvaraju ◽

Huzwah Khaza’ai ◽

Sharmili Vidyadaran ◽

Mohd Sokhini Abd Mutalib ◽

Vasudevan Ramachandran ◽

...

Keyword(s):

Vitamin E ◽

Cell Viability ◽

Neuronal Cells ◽

Positive Control ◽

Post Treatment ◽

Mitochondrial Activity ◽

Before And After ◽

Pre Treatment ◽

Tocotrienol Rich Fraction ◽

Major Mediator

Glutamate is the major mediator of excitatory signals in the mammalian central nervous system. Extreme amounts of glutamate in the extracellular spaces can lead to numerous neurodegenerative diseases. We aimed to clarify the potential of the following vitamin E isomers, tocotrienol-rich fraction (TRF) and α-tocopherol (α-TCP), as potent neuroprotective agents against glutamate-induced injury in neuronal SK-N-SH cells. Cells were treated before and after glutamate injury (pre- and post-treatment, respectively) with 100 - 300 ng/ml TRF/α-TCP. Exposure to 120 mM glutamate significantly reduced cell viability to 76 % and 79 % in the pre- and post-treatment studies, respectively; however, pre- and post-treatment with TRF/α-TCP attenuated the cytotoxic effect of glutamate. Compared to the positive control (glutamate-injured cells not treated with TRF/α-TCP), pre-treatment with 100, 200, and 300 ng/ml TRF significantly improved cell viability following glutamate injury to 95.2 %, 95.0 %, and 95.6 %, respectively (p < 0.05).The isomers not only conferred neuroprotection by enhancing mitochondrial activity and depleting free radical production, but also increased cell viability and recovery upon glutamate insult. Our results suggest that vitamin E has potent antioxidant potential for protecting against glutamate injury and recovering glutamate-injured neuronal cells. Our findings also indicate that both TRF and α-TCP could play key roles as anti-apoptotic agents with neuroprotective properties.

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The Effect of Mianserin on Lifespan of Caenorhabditis elegans is Abolished by Glucose

Current Aging Science ◽

10.2174/1874609813999210104203614 ◽

2021 ◽

Vol 13 ◽

Author(s):

Abdullah Almotayri ◽

Jency Thomas ◽

Mihiri Munasinghe ◽

Markandeya Jois

Keyword(s):

Caenorhabditis Elegans ◽

Scaffolding Protein ◽

Lifespan Extension ◽

Wild Type ◽

E Coli ◽

C Elegans ◽

Risk Of Death ◽

Increased Risk ◽

Antidepressant Use ◽

Extension Effect

Background: The antidepressant mianserin has been shown to extend the lifespan of Caenorhabditis elegans (C. elegans), a well-established model organism used in aging research. The extension of lifespan in C. elegans was shown to be dependent on increased expression of the scaffolding protein (ANK3/unc-44). In contrast, antidepressant use in humans is associated with an increased risk of death. The C. elegans in the laboratory are fed Escherichia coli (E. coli), a diet high in protein and low in carbohydrate, whereas a typical human diet is high in carbohydrates. We hypothesized that dietary carbohydrates might mitigate the lifespan-extension effect of mianserin. Objective: To investigate the effect of glucose added to the diet of C. elegans on the lifespan-extension effect of mianserin. Methods: Wild-type Bristol N2 and ANK3/unc-44 inactivating mutants were cultured on agar plates containing nematode growth medium and fed E. coli. Treatment groups included (C) control, (M50) 50 μM mianserin, (G) 73 mM glucose, and (M50G) 50 μM mianserin and 73 mM glucose. Lifespan was determined by monitoring the worms until they died. Statistical analysis was performed using the Kaplan-Meier version of the log-rank test. Results: Mianserin treatment resulted in a 12% increase in lifespan (P<0.05) of wild-type Bristol N2 worms but reduced lifespan by 6% in ANK3/unc-44 mutants, consistent with previous research. The addition of glucose to the diet reduced the lifespan of both strains of worms and abolished the lifespan-extension by mianserin. Conclusion: The addition of glucose to the diet of C. elegans abolishes the lifespan-extension effects of mianserin.

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Functional Redundancy of the B9 Proteins and Nephrocystins in Caenorhabditis elegans Ciliogenesis

Molecular Biology of the Cell ◽

10.1091/mbc.e07-10-1070 ◽

2008 ◽

Vol 19 (5) ◽

pp. 2154-2168 ◽

Cited By ~ 74

Author(s):

Corey L. Williams ◽

Marlene E. Winkelbauer ◽

Jenny C. Schafer ◽

Edward J. Michaud ◽

Bradley K. Yoder

Keyword(s):

Caenorhabditis Elegans ◽

Joubert Syndrome ◽

Cystic Kidney ◽

Basal Bodies ◽

The Novel ◽

C Elegans ◽

Human Genes ◽

Cilia Formation ◽

Strong Candidate ◽

Candidate Loci

Meckel-Gruber syndrome (MKS), nephronophthisis (NPHP), and Joubert syndrome (JBTS) are a group of heterogeneous cystic kidney disorders with partially overlapping loci. Many of the proteins associated with these diseases interact and localize to cilia and/or basal bodies. One of these proteins is MKS1, which is disrupted in some MKS patients and contains a B9 motif of unknown function that is found in two other mammalian proteins, B9D2 and B9D1. Caenorhabditis elegans also has three B9 proteins: XBX-7 (MKS1), TZA-1 (B9D2), and TZA-2 (B9D1). Herein, we report that the C. elegans B9 proteins form a complex that localizes to the base of cilia. Mutations in the B9 genes do not overtly affect cilia formation unless they are in combination with a mutation in nph-1 or nph-4, the homologues of human genes (NPHP1 and NPHP4, respectively) that are mutated in some NPHP patients. Our data indicate that the B9 proteins function redundantly with the nephrocystins to regulate the formation and/or maintenance of cilia and dendrites in the amphid and phasmid ciliated sensory neurons. Together, these data suggest that the human homologues of the novel B9 genes B9D2 and B9D1 will be strong candidate loci for pathologies in human MKS, NPHP, and JBTS.

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Characterization of Caenorhabditis elegans Homologs of the Down Syndrome Candidate Gene DYRK1A

Genetics ◽

10.1093/genetics/163.2.571 ◽

2003 ◽

Vol 163 (2) ◽

pp. 571-580 ◽

Cited By ~ 1

Author(s):

William B Raich ◽

Celine Moorman ◽

Clay O Lacefield ◽

Jonah Lehrer ◽

Dusan Bartsch ◽

...

Keyword(s):

Down Syndrome ◽

Caenorhabditis Elegans ◽

Trisomy 21 ◽

Gene Dosage ◽

Inducible Promoters ◽

C Elegans ◽

Dual Specificity ◽

Specificity Protein

Abstract The pathology of trisomy 21/Down syndrome includes cognitive and memory deficits. Increased expression of the dual-specificity protein kinase DYRK1A kinase (DYRK1A) appears to play a significant role in the neuropathology of Down syndrome. To shed light on the cellular role of DYRK1A and related genes we identified three DYRK/minibrain-like genes in the genome sequence of Caenorhabditis elegans, termed mbk-1, mbk-2, and hpk-1. We found these genes to be widely expressed and to localize to distinct subcellular compartments. We isolated deletion alleles in all three genes and show that loss of mbk-1, the gene most closely related to DYRK1A, causes no obvious defects, while another gene, mbk-2, is essential for viability. The overexpression of DYRK1A in Down syndrome led us to examine the effects of overexpression of its C. elegans ortholog mbk-1. We found that animals containing additional copies of the mbk-1 gene display behavioral defects in chemotaxis toward volatile chemoattractants and that the extent of these defects correlates with mbk-1 gene dosage. Using tissue-specific and inducible promoters, we show that additional copies of mbk-1 can impair olfaction cell-autonomously in mature, fully differentiated neurons and that this impairment is reversible. Our results suggest that increased gene dosage of human DYRK1A in trisomy 21 may disrupt the function of fully differentiated neurons and that this disruption is reversible.

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Maternal-effect lethal mutations on linkage group II of Caenorhabditis elegans.

Genetics ◽

10.1093/genetics/120.4.977 ◽

1988 ◽

Vol 120 (4) ◽

pp. 977-986

Author(s):

K J Kemphues ◽

M Kusch ◽

N Wolf

Keyword(s):

Caenorhabditis Elegans ◽

Linkage Group ◽

Maternal Effect ◽

Essential Genes ◽

The Other ◽

C Elegans ◽

Lethal Mutations ◽

Embryonic Lethal ◽

Embryonic Lethal Mutations ◽

F1 Progeny

Abstract We have analyzed a set of linkage group (LG) II maternal-effect lethal mutations in Caenorhabditis elegans isolated by a new screening procedure. Screens of 12,455 F1 progeny from mutagenized adults resulted in the recovery of 54 maternal-effect lethal mutations identifying 29 genes. Of the 54 mutations, 39 are strict maternal-effect mutations defining 17 genes. These 17 genes fall into two classes distinguished by frequency of mutation to strict maternal-effect lethality. The smaller class, comprised of four genes, mutated to strict maternal-effect lethality at a frequency close to 5 X 10(-4), a rate typical of essential genes in C. elegans. Two of these genes are expressed during oogenesis and required exclusively for embryogenesis (pure maternal genes), one appears to be required specifically for meiosis, and the fourth has a more complex pattern of expression. The other 13 genes were represented by only one or two strict maternal alleles each. Two of these are identical genes previously identified by nonmaternal embryonic lethal mutations. We interpret our results to mean that although many C. elegans genes can mutate to strict maternal-effect lethality, most genes mutate to that phenotype rarely. Pure maternal genes, however, are among a smaller class of genes that mutate to maternal-effect lethality at typical rates. If our interpretation is correct, we are near saturation for pure maternal genes in the region of LG II balanced by mnC1. We conclude that the number of pure maternal genes in C. elegans is small, being probably not much higher than 12.

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Improving skeleton algorithm for helping Caenorhabditis elegans trackers

Scientific Reports ◽

10.1038/s41598-020-79430-8 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Pablo E. Layana Castro ◽

Joan Carles Puchalt ◽

Antonio-José Sánchez-Salmerón

Keyword(s):

Computer Vision ◽

Caenorhabditis Elegans ◽

Transformation Function ◽

Simple Solution ◽

New Method ◽

Vision Systems ◽

Distance Transformation ◽

Automatic Computer ◽

C Elegans ◽

Computer Vision Systems

AbstractOne of the main problems when monitoring Caenorhabditis elegans nematodes (C. elegans) is tracking their poses by automatic computer vision systems. This is a challenge given the marked flexibility that their bodies present and the different poses that can be performed during their behaviour individually, which become even more complicated when worms aggregate with others while moving. This work proposes a simple solution by combining some computer vision techniques to help to determine certain worm poses and to identify each one during aggregation or in coiled shapes. This new method is based on the distance transformation function to obtain better worm skeletons. Experiments were performed with 205 plates, each with 10, 15, 30, 60 or 100 worms, which totals 100,000 worm poses approximately. A comparison of the proposed method was made to a classic skeletonisation method to find that 2196 problematic poses had improved by between 22% and 1% on average in the pose predictions of each worm.

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A survey of the kinome pharmacopeia reveals multiple scaffolds and targets for the development of novel anthelmintics

Scientific Reports ◽

10.1038/s41598-021-88150-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Jessica Knox ◽

Nicolas Joly ◽

Edmond M. Linossi ◽

José A. Carmona-Negrón ◽

Natalia Jura ◽

...

Keyword(s):

Caenorhabditis Elegans ◽

Developmental Delay ◽

Small Molecule ◽

Parasitic Nematode ◽

Kinase Inhibitor ◽

Binding Pocket ◽

Drug Binding ◽

Nematode Infection ◽

Selective Inhibitors ◽

C Elegans

AbstractOver one billion people are currently infected with a parasitic nematode. Symptoms can include anemia, malnutrition, developmental delay, and in severe cases, death. Resistance is emerging to the anthelmintics currently used to treat nematode infection, prompting the need to develop new anthelmintics. Towards this end, we identified a set of kinases that may be targeted in a nematode-selective manner. We first screened 2040 inhibitors of vertebrate kinases for those that impair the model nematode Caenorhabditis elegans. By determining whether the terminal phenotype induced by each kinase inhibitor matched that of the predicted target mutant in C. elegans, we identified 17 druggable nematode kinase targets. Of these, we found that nematode EGFR, MEK1, and PLK1 kinases have diverged from vertebrates within their drug-binding pocket. For each of these targets, we identified small molecule scaffolds that may be further modified to develop nematode-selective inhibitors. Nematode EGFR, MEK1, and PLK1 therefore represent key targets for the development of new anthelmintic medicines.

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